PRODUCT DETAILS
Active ingredient: Ibandronic acid, monosodium salt, monohydrate. One 150 mg film-coated tablet contains 168.75mg ibandronic acid, monosodium salt, monohydrate equivalent to 150 mg of ibandronic acid.

Ibandronic acid is a highly potent bisphosphonate belonging to the nitrogen-containing group of
bisphosphonates, which act on bone tissue and specifically inhibit osteoclast activity, It does not interfere with osteoclast recruitment. The selective action of ibandronic acid on bone tissue is based on the high affinity of this compound for hydroxyapatite, which represents the mineral matrix of the bone. Ibandronic acid reduces bone resorption, with no direct effect on bone formation. In postmenopausal women, it reduces the elevated rate of bone turnover towards premenopausal levels, leading to a progressive net gain in bone mass. Daily or intermittent administration of ibandronic acid results in reduced bone resorption as reflected in reduced levels of serum and urinary biochemical markers of bone turnover, increased BMD and a decreased incidence of fractures.

Presentation:

Each box contains One tablet in blister pack 150 mg film-coated tablet.

  Dosage and Administration

The recommended dose of Bonova for treatment is one 150 mg film-coated tablet once a month. The tablet should preferably be taken on the same date each month. Bonova should be taken 60 minutes before the first food or drink (other than water) of the day (see section 2.4.3 Interactions with other Medicinal Products and other Forms of Interaction, Drug-Food Interactions) or any other oral medication or supplementation (including calcium): — Tablets should be swallowed whole with a full glass of plain water (180 to 240 ml) while the patient is sitting or standing in an upright position. Patients should not lie down for 60 minutes after taking Bonova. — Plain water is the only drink that should be taken with Bonova. Please note that some mineral waters may have a higher concentration of calcium and therefore should not be used. — Patients should not chew or suck the tablet because of a potential for oropharyngeal ulceration. Patients should receive supplemental calcium or vitamin D if dietary intake is inadequate. In case a once-monthly dose is missed, patients should be instructed to take one Bonova 150 mg tablet the morning after the tablet is remembered, unless the time to the next scheduled dose is within 7 days. Patients should then return to taking their dose once a month on their originally scheduled date. If the next scheduled dose is within 7 days, patients should wait until their next dose and then continue taking one tablet once a month as originally scheduled. Patients should not take two 150 mg tablets within the same week.

  Side Effects

Treatment of postmenopausal osteoporosis
Once-monthly dosing
In a two-year study in postmenopausal women with osteoporosis (BM 16549) the overall safety of Bonova 150 mg once monthly and Bonova 2.5 mg daily was similar. The overall proportion of patients who experienced an adverse drug reaction, i.e. adverse event with a possible or probable relationship to trial medication, was 22.7 % and 25.0 % for Bonova 150mg once monthly and 21.5 % and 22.5 % for Bonova 2.5 mg daily after one and two years, respectively. The majority of adverse drug reactions were mild to moderate in intensity. Most cases did not lead to cessation of therapy.

Clinical Trials
Treatment of postmenopausal osteoporosis
Once-monthly dosing

In a two-year study in postmenopausal women with osteoporosis (BM 16549) the overall safety of Bonova 150 mg once monthly and Bonova 2.5 mg daily was similar. The overall proportion of patients who experienced an adverse drug reaction, i.e. adverse event with a possible or probable relationship to trial medication, was 22.7 % and 25.0 % for Bonova 150mg once monthly and 21.5 % and 22.5 % for Bonova 2.5 mg daily after one and two years, respectively. The majority of adverse drug reactions were mild to moderate in intensity. Most cases did not lead to cessation of therapy.

Tables 1 and 2 list adverse drug reactions occurring in more than I % of patients treated with Bonova 150 mg monthly or 2.5 mg daily in study BM 16549 and in patients treated with Bonova 2.5 mg daily in study MF 4411. The tables show the adverse drug reactions in the two studies that occurred with a higher incidence than in patients treated with placebo in study MF 4411. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Data at one year from BM 16549 are represented in Table 1 and cumulative data for the two years from
BM 16549 are represented in Table 2.

Adverse drug reactions occurring at a frequency of less than or equal to 1 % The following list provides
information on adverse drug reactions (considered possibly or probably related to treatment by the investigator) reported in study MF 4411 occurring more frequently with Bonova 2.5 mg daily than with placebo and study BM 16549 occurring more frequently with Bonova 150 mg once monthly than with Bonova 2.5 mg daily. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness:
Uncommon (1/100 — 1/1,000)
Gastrointestinal Disorders: gastritis, oesophagitis including oesophageal ulcerations or strictures, vomiting, dysphagia
Nervous System Disorders: dizziness
Musculoskeletal and Connective Tissue Disorders: back pain Rare (1/1,000 — 1/10,000)
Gastrointestinal Disorders: duodenitis
Immune System Disorders: hypersensitivity reactions Skin and Subcutaneous Tissue Disorders: angioedema, face oedema, urticaria Patients with a previous history of gastrointestinal disease including patients with peptic ulcer without recent bleeding or hospitalisation, and patients with dyspepsia or reflux controlled by medication were included in the once monthly treatment study. For
these patients, there was no difference in the incidence of upper gastrointestinal adverse events with the 150 mg once monthly regimen compared to the 2.5 mg daily regimen.

Laboratory Abnormalities
In the pivotal three-year study with Bonova 2.5 mg daily (MF 4411) there was no difference compared with placebo for laboratory abnormalities indicative of hepatic or renal dysfunction, impaired hematologic system, hypocalcemia or hypophosphatemia. Similarly, no differences were noted between the groups in study BM 16549 after one and two years.
Post Marketing Musculoskeletal and connective tissue disorders:
Osteonecrosis of the jaw has been reported very rarely in patients treated with ibandronic acid (refer to 2.4 Warnings and Precautions).
Eye disorders:
Ocular inflammation events such as uveitis, episcleritis and scleritis have been reported with bisphosphonates, including ibandronic acid. In some cases, these events did not resolve until the bisphosphonate was discontinued.

  Contraindications

Bonova is contraindicated in patients with known hypersensitivity to ibandronic acid or to any of the excipients. Bonova is contraindicated in patients with uncorrected hypocalcemia. As with all bisphosphonates indicated in the treatment of osteoporosis, pre-existing hypocalcemia needs to be corrected before initiating therapy with Bonova. As with several bisphosphonates, Bonova is contraindicated in patients with abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia (see section 2.4 Warnings and Precautions). Bonova is contraindicated in patients who are unable to stand or sit upright for at least 60 minutes (see sections 2.2 Dosage and Administration and 2.4 Warnings and Precautions).

  Use in Pregnancy and Lactation

In pregnancy:

Bonova should not be used during pregnancy.

There was no evidence for a direct fetal toxic or teratogenic effect of ibandronic acid in daily orally treated rats and rabbits and there were no adverse effects on the development in F1 offspring in rats. Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those observed with bisphosphonates as a class. They include a decreased number of implantation sites, interference with natural delivery (dystocia), and an increase in visceral variations (renal pelvis ureter syndrome). Specific studies for the monthly regimen have not been performed. There is no clinical experience with Bonova in pregnant women.

In lactation:
Bonova should not be used during lactation.

In lactating rats treated with 0.08 mg/kg/day iv. ibandronic acid, the highest concentration of ibandronic acid in breast milk was 8.1 ng/ml and was seen in the first 2 hours after i.v. administration. After 24 hours, the concentration in milk and plasma was similar, and corresponded to about 5 % of the concentration measured after 2 hours.

  Drug Interaction

It is likely that calcium supplements, antacids and some oral medications containing multivalent cations (such as aluminium, magnesium, iron) are likely to interfere with the absorption of Bonova. Therefore, patients must wait 60 minutes after taking Bonova before taking other oral medications. Pharmacokinetic interaction studies in postmenopausal women have demonstrated the absence of any interaction potential with tamoxifen or hormone replacement therapy (estrogen). No interaction was observed when co-administered with melphalan/prednisolone in patients with multiple myeloma. In healthy male volunteers and postmenopausal women, i.v. ranitidine caused an increase in ibandronic acid bioavailability of about 20 %, probably as a result of reduced gastric acidity. However, since this increase is within the normal range of the bioavailability of ibandronic acid, no dosage adjustment is required when Bonova is administered with H2-antagonists or other drugs which increase gastric pH.
In relation to disposition, no drug interactions of clinical significance are considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats. Furthermore, plasma protein binding is low at therapeutic concentrations and ibandronic acid is therefore unlikely to displace other drugs. Ibandronic acid is eliminated by renal excretion only and does not undergo any biotransformation. The secretory pathway appears not to include known acidic or basic transport systems involved in the excretion of other drugs. In a one-year study in postmenopausal women with osteoporosis (BM16549). the incidence of upper gastrointestinal events in patients concomitantly taking aspirin or NSAIDs was similar in patients taking Bonova 2.5mg daily or 150mg once monthly. Of over 1500 patients enrolled in study BM 16549 comparing monthly with daily dosing regimens of ibandronic acid, 14% of patients used histamine (H2) blockers or proton pump inhibitors. Among these patients, the incidence of upper gastrointestinal events in the patients treated with Bonova 150 mg once monthly was similar to that in patients treated with Bonova 2.5 mg daily.

  Over Dosage

No specific information is available on the treatment of overdosage with Bonova. However, oral overdosage may result in upper gastrointestinal adverse events, such as upset stomach, heartburn, esophagitis, gastritis, or ulcer. Milk or antacids should be given to bind Bonova. Owing to the risk of esophageal irritation, vomiting should not be induced and the patient should remain fully upright.

  Storage

Keep in a cool and dry place. Do not store above 30°C.
Keep out of reach of children. 123

  Commercial Pack

Bonova® 150 mg tablet: Each box contains One tablet in blister pack

  Others
  • Bonova®